Mitochondrial abnormalities in Alzheimer's disease

Keisuke Hirai, Gjumrakch Aliev, Akihiko Nunomura, Hisashi Fujioka, Robert L. Russell, Craig S. Atwood, Anne B. Johnson, Yvonne Kress, Harry V. Vinters, Massimo Tabaton, Shun Shimohama, Adam D. Cash, Sandra L. Siedlak, Peggy L.R. Harris, Paul K. Jones, Robert B. Petersen, George Perry, Mark A. Smith

Research output: Contribution to journalArticlepeer-review

1123 Scopus citations


The finding that oxidative damage, including that to nucleic acids, in Alzheimer's disease is primarily limited to the cytoplasm of susceptible neuronal populations suggests that mitochondrial abnormalities might be part of the spectrum of chronic oxidative stress of Alzheimer's disease. In this study, we used in situ hybridization to mitochondrial DNA (mtDNA), immunocytochemistry of cytochrome oxidase, and morphometry of electron micrographs of biopsy specimens to determine whether there are mitochondrial abnormalities in Alzheimer's disease and their relationship to oxidative damage marked by 8-hydroxyguanosine and nitrotyrosine. We found that the same neurons showing increased oxidative damage in Alzheimer's disease have a striking and significant increase in mtDNA and cytochrome oxidase. Surprisingly, much of the mtDNA and cytochrome oxidase is found in the neuronal cytoplasm and in the case of mtDNA, the vacuoles associated with lipofuscin. Morphometric analysis showed that mitochondria are significantly reduced in Alzheimer's disease. The relationship shown here between the site and extent of mitochondrial abnormalities and oxidative damage suggests an intimate and early association between these features in Alzheimer's disease.

Original languageEnglish
Pages (from-to)3017-3023
Number of pages7
JournalJournal of Neuroscience
Issue number9
StatePublished - May 1 2001


  • Alzheimer's disease
  • Free radicals
  • Metabolism
  • Mitochondria
  • Neurodegeneration
  • Oxidative stress


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